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Investigating astrocyte status in alcohol use disorder with the novel positron emission tomography (PET) tracer [11C]SL25.1188.

Award Number: R21AA026680
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2019
PERIOD OF PERFORMANCE END DATE: 10/31/2023

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Investigating astrocyte status in alcohol use disorder with the novel positron emission tomography (PET) tracer [11C]SL25.1188. - PROJECT SUMMARY Background and Objective: Alcohol use disorder (AUD) can be a treatable condition, but relapse rates are still high and new therapeutic targets important to the pathophysiology need to be identified. Emerging pre- clinical and human postmortem data implicate astroglia, the most abundant glial cell in brain, in AUD behavior and associated brain damage. Although controversial, we believe that the astroglial response to chronic brain insult (e.g., in AUD) is largely and normally protective (i.e., not harmful) by supporting neuronal metabolic function and integrity. Since the status of astroglia in brain of persons with AUD is uncertain, and may even be compromised, our overall Objective is to establish whether the astroglial cell is deficient, or not, in living brain of persons with AUD. We expect that the obtained results will help guide therapeutic efforts. Specific Aims and Hypotheses: We aim to establish whether brain levels of an astroglial marker, the enzyme monoamine oxidase B (MAO-B), are lower in AUD than those in healthy control subjects (and may recover during protracted abstinence). Our directional working hypothesis is based on some postmortem human brain data suggesting that brain astroglial integrity might be lower than normal in AUD. Design: To measure astroglial status we will measure binding of [11C]SL25.1188, a third generation PET (positron emission tomography) radiotracer selective for MAO-B, which we recently developed for use in the human. 25 persons with AUD in early abstinence (3-7 days) 15 of which are estimated to completed a scan during protracted abstinence (~21 days) and 25 matched control subjects will be enrolled. We will also examine the relationship between astroglial activation (inferred from PET data) and peripheral blood measures of immune markers and explore whether these might be related to behaviour (e.g. relapse, craving, withdrawal). Relevance: Our team is unique in combining extensive experience in measuring glial proteins in both postmortem and living brain of persons with substance use disorders and in developing/using (to our knowledge) the only third generation radiolabeled astroglial marker in human PET brain imaging investigations. The obtained results will represent the first step in guiding therapeutic efforts targeted at the brain astroglial cell in AUD while at the same time exploring the relationship between brain and peripheral (blood) markers in this condition. The latter effort is innovative and will address the unmet need for identification of simple, noninvasive and inexpensive pathophysiologically relevant peripheral biomarkers of CNS “damage”.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2020	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON			CAN	Alcohol Research Programs	000	2	4/4/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2020	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON			CAN	Alcohol Research Programs	000	2	1/24/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON			CAN	Alcohol Research Programs	000	2	12/20/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $139,953 )
2020	2020	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON	M6J 1H4		CAN	Alcohol Research Programs	000	2	1/24/2020	NON-COMPETING CONTINUATION	$139,953
														Subtotal = $139,953

Issue Date FY: 2019 ( Subtotal = $143,368 )
2019	2019	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON	M6J 1H4		CAN	Alcohol Research Programs	000	1	1/22/2019	NEW	$143,368
														Subtotal = $143,368

Grand Total All Awards = $283,321

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Investigating astrocyte status in alcohol use disorder with the novel positron emission tomography (PET) tracer [11C]SL25.1188.

Award Number: R21AA026680

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2019

PERIOD OF PERFORMANCE END DATE: 10/31/2023

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